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Introduction: Data from patient cohorts and mouse models of atopic dermatitis, food allergy and asthma strongly support a role for chitinase-3-like-1 protein (CHI3L1) in allergic disease. Methods: To address whether Chi3l1 also contributes to TH2 responses following nematode infection, we infected Chi3l1-/- mice with Heligmosomoides polygyrus (Hp) and analyzed T cell responses. Results: As anticipated, we observed impaired TH2 responses in Hp-infected Chi3l1-/- mice. However, we also found that T cell intrinsic expression of Chi3l1 was required for ICOS upregulation following activation of naïve CD4 T cells and was necessary for the development of the IL-4+ TFH subset, which supports germinal center B cell reactions and IgE responses. We also observed roles for Chi3l1 in TFH, germinal center B cell, and IgE responses to alum-adjuvanted vaccination. While Chi3l1 was critical for IgE humoral responses it was not required for vaccine or infection-induced IgG1 responses. Discussion: These results suggest that Chi3l1 modulates IgE responses, which are known to be highly dependent on IL-4-producing TFH cells. [ABSTRACT FROM AUTHOR]

The article presents the discussion on transgenic mice overexpressing ORMDL3 spontaneously develop features of airway hyperresponsiveness and airway remodeling. Topics include asthma genome-wide association studies, expression quantitative trait loci mapping, and allelic imbalance assays; and using an unbiased mass spectrometry approach, SERCA2 being identified as an ORMDL3-interacting protein.

Introduction: Data from patient cohorts and mouse models of atopic dermatitis, food allergy and asthma strongly support a role for chitinase-3-like-1 protein (CHI3L1) in allergic disease., Methods: To address whether Chi3l1 also contributes to T H 2 responses following nematode infection, we infected Chi3l1 -/- mice with Heligmosomoides polygyrus ( Hp ) and analyzed T cell responses., Results: As anticipated, we observed impaired T H 2 responses in Hp -infected Chi3l1 -/- mice. However, we also found that T cell intrinsic expression of Chi3l1 was required for ICOS upregulation following activation of naïve CD4 T cells and was necessary for the development of the IL-4 + T FH subset, which supports germinal center B cell reactions and IgE responses. We also observed roles for Chi3l1 in T FH , germinal center B cell, and IgE responses to alum-adjuvanted vaccination. While Chi3l1 was critical for IgE humoral responses it was not required for vaccine or infection-induced IgG1 responses., Discussion: These results suggest that Chi3l1 modulates IgE responses, which are known to be highly dependent on IL-4-producing T FH cells., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Curtiss, Rosenberg, Scharer, Mousseau, Benavides, Bradley, León, Steele, Randall and Lund.)